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Biomedical subjects

D R Moore

Publications and source records attributed to D R Moore.

At least 19 recordsLinked to original sources
PubMed2006

Reliable identification of the auditory thalamus using multi-modal structural analyses.

The medial geniculate body (MGB) of the thalamus is a key component of the auditory system. It is involved in relaying and transforming auditory information to the cortex and in top-down modulation of processing in the midbrain, brainstem, and ear. Functional imaging investigations of this region in humans, however, have been limited by the difficulty of distinguishing MGB from other thalamic nuclei. Here, we introduce two methods for reliably delineating MGB anatomically in individuals based on conventional and diffusion MRI data. The first uses high-resolution proton density weighted scanning optimized for subcortical grey-white contrast. The second uses diffusion-weighted imaging and probabilistic tractography to automatically segment the medial and lateral geniculate nuclei from surrounding structures based on their distinctive patterns of connectivity to the rest of the brain. Both methods produce highly replicable results that are consistent with published atlases. Importantly, both methods rely on commonly available imaging sequences and standard hardware, a significant advantage over previously described approaches. In addition to providing useful approaches for identifying the MGB and LGN in vivo, our study offers further validation of diffusion tractography for the parcellation of grey matter regions on the basis of their connectivity patterns.

Adult↗
PubMed2005

Exactly which synephrine alkaloids does Citrus aurantium (bitter orange) contain?

Following the withdrawal of ephedrine from the dietary supplement marketplace sales of products containing Citrus aurantium (CA) (bitter orange) for weight loss are believed to have increased dramatically. CA contains a number of constituents speculated to lead to weight loss, of which the most frequently cited constituent is synephrine. Concerns have been raised about the safety of products containing synephrine. To develop an adequate basis for clinical and public health recommendations, it is necessary to understand the nature of the synephrine alkaloids in CA. There are six possible isomers of synephrine (para, meta, ortho; and for each a d or l form). Some authors have stated that CA contains only p-synephrine, whereas other authors have stated that CA contains m-synephrine. This is an important distinction because the two molecules have different pharmacologic properties, which may differentially affect safety and efficacy. We are unable to identify published data that explicitly show whether CA contains p-synephrine, m-synephrine, or both. In this brief report, we show that at least one product purportedly containing synephrine alkaloids from CA contains both p-synephrine and m-synephrine. We believe this justifies further investigation into which synephrine alkaloids are present in CA and products purportedly containing synephrine alkaloids from CA and the relative quantities of each of the different isomers.

Alkaloids↗
PubMed2001

Hearing: cortical activation does matter.

Lesion studies have suggested that the auditory cortex may not be involved in many aspects of hearing. A recent report casts doubt on this long-held view by showing that reversible inactivation of the auditory cortex leads to a transient impairment in tone detection and frequency discrimination.

Animals↗
PubMed2001

Single-site beta-diiminate zinc catalysts for the alternating copolymerization of CO2 and epoxides: catalyst synthesis and unprecedented polymerization activity.

Synthetic routes to zinc beta-diiminate complexes are reported. The synthesis of 11 beta-diimine [(BDI)-H] ligands, with varying N-aryl substituents and bridging structures, is described. These ligands are converted to (BDI)ZnX complexes (X = OAc, Et, N(SiMe3)2, Br, Cl, OH, OMe, O(i)Pr). X-ray structural data revealed that all zinc complexes examined exist as micro-X-bridged dimers in the solid state, with the exception of the zinc ethyl and amido complexes which were monomeric. Complexes of the form (BDI)ZnOR (R = alkyl, acyl) and (BDI)ZnN(SiMe3)2 are highly active catalysts for the alternating copolymerization of epoxides and CO2. Copolymerizations of cyclohexene oxide (CHO) and CO2 with (BDI-1)ZnX [(BDI-1) = 2-((2,6-diisopropylphenyl)amido)-4-((2,6-diisopropylphenyl)imino)-2-pentene)] and (BDI-2)ZnX [(BDI-2) = 2-((2,6-diethylphenyl)amido)-4-((2,6-diethylphenyl)imino)-2-pentene)], where X = OAc, Et, N(SiMe3)2, Br, Cl, OH, OMe, O(i)Pr, were attempted at 50 degrees C and 100 psi CO2. Complexes with X = OAc, N(SiMe3)2, OMe, O(i)Pr all produced polycarbonate by the alternated insertion of CHO and CO2 with similar catalytic activities, comparable molecular weights, and narrow molecular weight distributions (MWD approximately 1.1), indicating the copolymerizations are living. Furthermore, ligand effects were shown to dramatically influence the polymerization activity as minor steric changes accelerated or terminated the polymerization activity.

Journal Article↗
PubMed2001

Polymerization of lactide with zinc and magnesium beta-diiminate complexes: stereocontrol and mechanism.

A series of zinc(II) and magnesium(II) alkoxides based upon a beta-diiminate ligand framework has been prepared. [(BDI-1)ZnO(i)Pr](2) [(BDI-1) = 2-((2,6-diisopropylphenyl)amido)-4-((2,6-diisopropylphenyl)imino)-2-pentene] exhibited the highest activity and stereoselectivity of the zinc complexes studied for the polymerization of rac- and meso-lactide to poly(lactic acid) (PLA). [(BDI-1)ZnO(i)()Pr](2) polymerized (S,S)-lactide to isotactic PLA without epimerization of the monomer, rac-lactide to heterotactic PLA (P(r) = 0.94 at 0 degrees C), and meso-lactide to syndiotactic PLA (P(r) = 0.76 at 0 degrees C). The polymerizations are living, as evidenced by the narrow polydispersities of the isolated polymers in addition to the linear nature of number average molecular weight versus conversion plots and monomer-to-catalyst ratios. The substituents on the beta-diiminate ligand exert a significant influence upon the course of the polymerizations, affecting both the degree of stereoselectivity and the rate of polymerization. Kinetic studies with [(BDI-1)ZnO(i)Pr](2) indicate that the polymerizations are first order with respect to monomer (rac-lactide) and 1.56 order in catalyst. Polymerization experiments with [(BDI-1)MgO(i)Pr](2) revealed that this complex is extremely fast for the polymerization of rac-lactide, polymerizing 500 equiv in 96% yield in less than 5 min at 20 degrees C.

Biocompatible Materials↗
PubMed2001

A predictive model of mercury fish tissue concentrations for the southeastern United States.

We developed a statistical model for predicting mercury concentrations in fish tissue in four southeastern states in the United States with an emphasis on identifying important predictor variables. A number of variables that could influence mercury fish tissue concentration, including proximity to sources of mercury, environmental factors affecting mercury movement and transformation, and factors affecting mercury accumulation, were considered. The model consists of three components using classification and regression three modeling, generalized additive modeling, and universal kriging, respectively. Each modeling component accounts for a different level of variation in fish tissue mercury concentration. Important factors for predicting mercury fish tissue concentrations are: (1) location, (2) species, (3) water body pH, and (4) fish weight. South central Arkansas and southeast Mississippi are the two "hot spots" with high fish tissue mercury concentrations. In addition, relatively high mercury levels were found near the Arkansas-Louisiana border and the mid-section of Mississippi.

Animals↗
PubMed2001

Free radical generation in the cochlea during combined exposure to noise and carbon monoxide: an electrophysiological and an EPR study.

Ototoxicity following combined exposure to noise and carbon monoxide (CO) is known to result in more severe permanent threshold shifts than exposure to noise alone. We have previously demonstrated that such potentiation of noise-induced auditory impairment by CO can be prevented by the administration of a nitrone spin-trapping agent. Although such protection implicates injury via free radical pathways, drug-induced protection does not provide direct evidence for the presence of free radicals in the cochlea. The objective of this study was to demonstrate the actual presence of nitrone spin adducts in the cochlea following simultaneous exposure to noise and CO. Using electrophysiological end-points, the protective effects of the nitrone spin-trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) were assessed following combined exposure of adult male Long Evans hooded rats to noise and CO. In addition, an ex-vivo evaluation of POBN spin adducts was done by electron paramagnetic resonance spectroscopy (EPR). The noise used was octave band noise with center frequency 13.6 kHz at 100 dB(Lin) for a duration of 2 h. The level of CO used was 1200 ppm. Electrophysiological results demonstrate that POBN protects against combined exposure to noise plus CO. The EPR study demonstrates POBN spin adducts in the cochleae of animals exposed to noise plus CO. Therefore, this study provides evidence to the hypothesis that ototoxicity due to noise plus CO exposure is mediated via free radicals.

Animals↗
PubMed2001

Interpersonal processes and psychopathology among expectant and nonexpectant adolescent couples.

This study examined the interpersonal and psychological functioning of expectant and nonexpectant adolescent couples. Interpersonal processes were assessed using the Structural Analysis of Social Behavior (L. S. Benjamin, 1974) and psychological functioning was assessed using the Diagnostic Interview for Children and Adolescents--Revised (W. Reich, 1991). Compared with their nonexpectant peers, expectant couples exhibited higher rates of negative interpersonal processes, including demand-withdraw behaviors and lower rates of positive interpersonal processes. Expectant males reported higher rates of behavior disorders, substance use disorders, and internalizing disorders than nonexpectant males. Higher rates of substance-use disorders mediated the effect of expectancy status on demand-withdraw behavior. Results help clarify the links between the psychological risks associated with adolescent pregnancy and the interpersonal functioning of young expectant couples.

Adolescent↗
PubMed2001

Development of brain-derived neurotrophic factor and neurotrophin-3 immunoreactivity in the lower auditory brainstem of the postnatal gerbil.

The localization of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in the gerbil auditory brainstem was studied during normal postnatal development. The principal objective of this paper was to compare the developmental distribution of BDNF and NT-3 proteins to the known developmental distribution of their cognate, high-affinity tyrosine kinase receptors. BDNF and NT-3 proteins were localized using standard immunohistochemistry. No specific immunoreactivity for BDNF or NT-3 was detected on the day of birth (P0) in any auditory structure, although fibers comprising the spinal tract of the Vth cranial nerve were well labelled with antibodies against BDNF. Diffuse immunoreactivity for both BDNF and NT-3 was first detected at P3 in the cochlear nucleus and in several second order auditory nuclei in the superior olivary complex. This diffuse immunoreactivity became clustered and restricted to neuronal cell bodies by P10. Immunoreactivity for both BDNF and NT-3 transiently disappeared in the lateral and medial superior olivary nuclei at P10. However, neurons in the medial nucleus of the trapezoid body remained immunopositive for both BDNF and NT-3. Fibers in the trapezoid body were labelled with BDNF immunoreactivity by P12. Between P12 and P15, the distribution of BDNF and NT-3 immunoreactivity in the cochlear nucleus and superior olivary complex became comparable to adult (P140) immunolabel. These results show that the normal developmental distribution of the neurotrophins BDNF and NT-3 in the lower auditory brainstem occurs during the first two postnatal weeks in parallel with the developmental expression of their cognate receptors, trkB and trkC.

Animals↗
PubMed2001

Direct administration of interleukin-1 and interferon-gamma to rat pancreas leads to the in vivo production of nitric oxide and expression of inducible nitric oxide synthase and inducible cyclooxygenase.

INTRODUCTION: Proinflammatory cytokines may play a pivotal role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). In vitro, the formation of nitric oxide (NO) catalyzed by inducible NO synthase (iNOS) has been shown to be involved in the cytotoxic effects of cytokines on pancreatic beta cells. Cytokines have also been shown to cause the expression of inducible cyclooxygenase (COX-2) in isolated islets. AIMS: To describe a novel in vivo model that allows investigation of the effects of direct cytokine administration to the pancreas. METHODOLOGY AND RESULTS: By using this method, we demonstrate that administration of interleukin-1beta and interferon-gamma to rat pancreas results in the generation of NO in the treated pancreata as detected by NO trapping and electron paramagnetic resonance spectroscopy. Beta cells were identified as the source of the formed NO. Reverse transcription and polymerase chain reaction analyses showed that administration of cytokines to the pancreas leads to the expression of iNOS and COX-2 mRNA in the pancreas tissue as well as the islets isolated from such tissues. The compound phenyl N-tert-butylnitrone, which protects mice against streptozotocin-induced IDDM, inhibits NO formation and downregulates both iNOS and COX-2 mRNA levels.

Alloxan↗
PubMed2000

Plasticity in the neural coding of auditory space in the mammalian brain.

Sound localization relies on the neural processing of monaural and binaural spatial cues that arise from the way sounds interact with the head and external ears. Neurophysiological studies of animals raised with abnormal sensory inputs show that the map of auditory space in the superior colliculus is shaped during development by both auditory and visual experience. An example of this plasticity is provided by monaural occlusion during infancy, which leads to compensatory changes in auditory spatial tuning that tend to preserve the alignment between the neural representations of visual and auditory space. Adaptive changes also take place in sound localization behavior, as demonstrated by the fact that ferrets raised and tested with one ear plugged learn to localize as accurately as control animals. In both cases, these adjustments may involve greater use of monaural spectral cues provided by the other ear. Although plasticity in the auditory space map seems to be restricted to development, adult ferrets show some recovery of sound localization behavior after long-term monaural occlusion. The capacity for behavioral adaptation is, however, task dependent, because auditory spatial acuity and binaural unmasking (a measure of the spatial contribution to the "cocktail party effect") are permanently impaired by chronically plugging one ear, both in infancy but especially in adulthood. Experience-induced plasticity allows the neural circuitry underlying sound localization to be customized to individual characteristics, such as the size and shape of the head and ears, and to compensate for natural conductive hearing losses, including those associated with middle ear disease in infancy.

Adaptation, Physiological↗
PubMed2000

Auditory neuroscience: is speech special?

Speech is thought to be perceived and processed in a unique way by the auditory system of the brain. A recent study has provided evidence that a part of the brain's temporal lobe is specifically responsive to speech and other vocal stimuli.

Acoustic Stimulation↗
PubMed2000

Aromatic hydroxylation in PBN spin trapping by hydroxyl radicals and cytochrome P-450.

Phenyl N-tert-butylnitrone (PBN) is widely used as a spin trapping agent, but is not useful detecting hydroxyl radicals because the resulting spin adduct is unstable. However, hydroxyl radicals could attack the phenyl ring to form stable phenolic products with no electron paramagnetic resonance signal, and this possibility was investigated in the present studies. When PBN was added to a Fenton reaction system composed of 25 mM H(2)O(2) and 0.1 mM FeSO(4), 4-hydroxyPBN was the primary product detected, and benzoic acid was a minor product. When the Fe(2+) concentration was increased to 1.0 mM, 4-hydroxyPBN concentrations increased dramatically, and smaller amounts of benzoic acid and 2-hydroxyPBN were also formed. Although PBN is extensively metabolized after administration to animals, its metabolites have not been identified. When PBN was incubated with rat liver microsomes and a reduced nicotinamide adenine dinculeotide phosphate (NADPH)-generating system, 4-hydroxyPBN was the only metabolite detected. When PBN was given to rats, both free and conjugated 4-hydroxyPBN were readily detected in liver extracts, bile, urine, and plasma. Because 4-hydroxyPBN is the major metabolite of PBN and circulates in body fluids, it may contribute to the pharmacological properties of PBN. But 4-hydroxyPBN formation cannot be used to demonstrate hydroxyl radical formation in vivo because of its enzymatic formation.

Animals↗
PubMed2000

Down-regulation of inhibition following unilateral deafening.

Physiological and neurochemical experiments described here suggest that unilateral deafening causes a reduction in inhibition in the adult gerbil inferior colliculus (IC) contralateral to the deafened ear. Multiple-unit recordings were made from single electrode penetrations in the IC prior to and directly after contralateral cochlear ablation. These recordings showed up to 60% increases in the proportion of sampled loci at which neural activity excited by ipsilateral stimulation was observed after the ablation. Novel excitatory responses were evident within minutes of the ablation. Western blotting for glutamic acid decarboxylase protein levels showed significant decreases in the IC contralateral to cochlear ablation, relative to those in the ipsilateral IC, at 24 h and 7 days survival after the ablation. Four hour or 1 year survival post-ablation did not produce significant contralateral/ipsilateral differences in relation to the control group. Taken together, these results suggest the presence of at least two, short-term mechanisms involved in the central response to cochlear removal, both of which appear to implicate a decreased inhibitory influence. One is a very rapid, stimulus-related, functional unmasking. The other is a more delayed reduction in the capacity of gamma-aminobutyric acid synthesis in the IC.

Animals↗
PubMed2000

Age-related improvements in auditory backward and simultaneous masking in 6- to 10-year-old children.

This study investigated the development of auditory frequency and temporal resolution using simultaneous and backward masking of a tone by a noise. The participants were 6- to 10-year-old children and adults. On the measure of frequency resolution (the difference in the detection threshold for a tone presented either in a bandpass noise or in a spectrally notched noise), 6-year-old children performed as well as adults. However, for the backward masking task, 6-year-olds had, on average, 34 dB higher thresholds than adults. A negative exponential decay function fitted to the backward masking data for subjects of all ages indicated that adult-like temporal resolution may not be reached until about 11 years of age. These results show that, measured by masking, frequency resolution has reached adult-like performance by 6 years of age, whereas temporal resolution develops beyond 10 years of age. Six-year-old children were also assessed with tests of cognitive ability. Improvements in both frequency and temporal resolution were found with increasing IQ score.

Adult↗
PubMed2000

Bone morphogenetic protein inhibits ovarian androgen production.

Bone morphogenetic proteins (BMPs), members of the transforming growth factor beta superfamily, were recently shown to be expressed and to regulate steroidogenesis in rat ovarian tissue. The purpose of this study was to investigate the effect of BMP-4 on androgen production in a human ovarian theca-like tumor (HOTT) cell culture model. We have previously demonstrated the usefulness of these cells as a model for human thecal cells. HOTT cells respond to protein kinase A agonists by increased production of androstenedione and with an induction of steroid-metabolizing enzymes. In this investigation, HOTT cells were treated with forskolin or dibutyryl cyclic AMP (dbcAMP) in the presence or absence of various concentrations of BMP-4. The accumulation of androstenedione, progesterone, and 17alpha-hydroxyprogesterone (17OHP) in the incubation medium was measured by RIA. The expression of 17alpha-hydroxylase (CYP17), 3beta-hydroxysteroid dehydrogenase (3betaHSD), cholesterol side-chain cleavage (CYP11A1), and steroidogenic acute regulatory (StAR) protein was determined by protein immunoblotting analysis using specific rabbit polyclonal antibodies. We also examined the expression of BMP receptor subtypes in our HOTT cells using RT-PCR. In cells treated with medium alone, steroid accumulation and steroid enzyme expression was unchanged. In cells treated with BMP alone there was a modest decrease in androstenedione secretion. In the presence of forskolin, HOTT cell production of androstenedione, 17OHP, and progesterone increased by approximately 4.5-, 35-, and 3-fold, respectively. In contrast, BMP-4 decreased forskolin-stimulated HOTT cell secretion of androstenedione and 17OHP by 50% but increased progesterone production 3-fold above forskolin treatment alone. Forskolin treatment led to an increase in CYP17, CYP11A1, 3betaHSD, and StAR protein expression. BMP-4 markedly inhibited forskolin stimulation of CYP17 expression but had little effect on 3betaHSD, CYP11A1, or StAR protein levels. Similar results were observed with the cAMP analog dbcAMP. In addition, BMP-4 inhibited basal and forskolin stimulation of CYP17 messenger RNA expression as determined by RNase protection assay. Other members of the transforming growth factor beta superfamily, including activin and inhibin, had minimal effect on androstenedione production in the absence of forskolin. In the presence of forskolin, activin inhibited androstenedione production by 80%. Activin also inhibited forskolin induction of CYP17 protein expression as determined by Western analysis. We identified the presence of messenger RNA for three BMP receptors (BMP-IA, BMP-IB, and BMP-II) in the HOTT cells model. In conclusion, BMP-4 inhibits HOTT cell expression of CYP17, leading to an alteration of steroidogenic pathway resulting in reduced androstenedione accumulation and increased progesterone production. These effects of BMP-4 seem similar to those caused by activin, another member of the transforming growth factor-beta superfamily of proteins.

Androgens↗
PubMed2000

Pronounced hepatic free radical formation precedes pathological liver injury in ethanol-fed rats.

BACKGROUND: The role of free radicals in alcoholic liver injury remains uncertain. These experiments were conducted to measure radical formation in rats that were fed alcohol along with either fish oil or saturated fats, which cause different types of liver pathology. METHODS: Liquid diets containing alcohol or isocaloric dextrose were administered to rats by intragastric infusion for 2 weeks. Radical intermediates detected by spin trapping were measured in bile. RESULTS: In rats that were fed alcohol plus fish oil, biliary concentrations of trapped radicals, which most likely originated from lipids, were 6-fold higher than in controls that were fed fish oil plus dextrose. High rates of radical formation persisted 24 hr after alcohol withdrawal, when all alcohol had been metabolized. In contrast, diets containing alcohol and medium chain triglycerides did not stimulate lipid radical formation. CONCLUSIONS: High rates of lipid radical formation were observed only in rats that were fed alcohol in combination with a fish oil diet, and a persistent flux of radical formation continued after alcohol withdrawal. These radical phenomena precede serious liver pathology, which develops after longer periods of fish oil plus alcohol diets.

Animals↗